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Measures of obesity, including body mass index (BMI) and waist circumference (WC), do not fully capture the complexity of obesity-related health risks. This study identified distinct classes of obesity-related characteristics and evaluated their associations with BMI, WC, and percent body fat (%BF) using cross-sectional data from 30,096 participants aged 45-85 in the Canadian Longitudinal Study on Aging (2011-2015). Sixteen obesity-related variables, including behavioural, metabolic, physical health, and mental health/social factors, were included in a latent class analysis to identify distinct classes of participants. Adjusted odds ratios (OR) were estimated from logistic regression for associations between each class and obesity defined by BMI, WC and %BF. Six latent classes were identified: "low-risk" (39.8%), "cardiovascular risk" (19.4%), "metabolic risk" (16.9%), "sleep and mental health risk" (12.1%), "multiple and complex risk" (6.7%), and "cardiometabolic risk" (5.1%). Compared to "low-risk", all classes had increased odds of BMI-, WC- and %BF-defined obesity. For example, the "complex and multiple risk" class was associated with obesity by BMI (OR: 10.70, 95% confidence interval (CI): 9.51, 12.04), WC (OR: 9.21, 95% CI: 8,15, 10,41) and %BF (OR: 7.54, 95% CI: 6.21, 9.16). Distinct classes of obesity-related characteristics were identified and were strongly associated with obesity defined by multiple measures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The trajectory of frailty in older adults is important to public health; therefore, markers that may help predict this and other important outcomes could be beneficial. Epigenetic clocks have been developed and are associated with various health-related outcomes and sociodemographic factors, but associations with frailty are poorly described. Further, it is uncertain whether newer generations of epigenetic clocks, trained on variables other than chronological age, would be more strongly associated with frailty than earlier developed clocks. Using data from the Canadian Longitudinal Study on Aging (CLSA), we tested the hypothesis that clocks trained on phenotypic markers of health or mortality (i.e., Dunedin PoAm, GrimAge, PhenoAge and Zhang in Nat Commun 8:14617, 2017) would best predict changes in a 76-item frailty index (FI) over a 3-year interval, as compared to clocks trained on chronological age (i.e., Hannum in Mol Cell 49:359-367, 2013, Horvath in Genome Biol 14:R115, 2013, Lin in Aging 8:394-401, 2016, and Yang Genome Biol 17:205, 2016)., Results: We show that in 1446 participants, phenotype/mortality-trained clocks outperformed age-trained clocks with regard to the association with baseline frailty (mean = 0.141, SD = 0.075), the greatest of which is GrimAge, where a 1-SD increase in ΔGrimAge (i.e., the difference from chronological age) was associated with a 0.020 increase in frailty (95% CI 0.016, 0.024), or ~ 27% relative to the SD in frailty. Only GrimAge and Hannum (Mol Cell 49:359-367, 2013) were significantly associated with change in frailty over time, where a 1-SD increase in ΔGrimAge and ΔHannum 2013 was associated with a 0.0030 (95% CI 0.0007, 0.0050) and 0.0028 (95% CI 0.0007, 0.0050) increase over 3 years, respectively, or ~ 7% relative to the SD in frailty change., Conclusion: Both prevalence and change in frailty are associated with increased epigenetic age. However, not all clocks are equally sensitive to these outcomes and depend on their underlying relationship with chronological age, healthspan and lifespan. Certain clocks were significantly associated with relatively short-term changes in frailty, thereby supporting their utility in initiatives and interventions to promote healthy aging., (© 2021. The Author(s).)

The challenge of distinguishing between changes attributable to ageing and those attributable to pathology is even greater for the immune system than for many other organs, and this is especially true for myeloid-derived suppressor cells (MDSCs). Hematopoiesis is different in older adults with a bias towards myelopoiesis, and older adults also manifest "inflammageing" exacerbated by disease and contributing to MDSC induction. Hence, at least in humans, one can only investigate MDSCs in the context of ageing and disease states, and not in the context of ageing processes per se. This contribution provides a brief overview of the literature on MDSCs and ageing in humans., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Many studies have shown that estimates of biological age (BA) can predict health-related outcomes in older adults. Often, researchers employ multiple measures belonging to a variety of biological/physiological systems, and assess the validity of BA estimates by how well they approximate chronological age (CA). However, it is not clear whether this is the best approach for judging a BA estimate, or whether certain groups of measures are more informative to this end. Using data from the Canadian Longitudinal Study on Aging, we composed panels of biological measures based on the physiological systems/domains they belong to (blood, organ function, physical/cognitive performance), and also composed a panel of measures that optimized the association of BA with CA. We then compared BA estimates for each according to their association with CA and health-related outcomes, including frailty, multimorbidity, chronic condition domains, disability, and health care utilization. Although BA estimated using all 40 measures (r = 0.74) or our age-optimized panel (r = 0.77) most closely approximated CA, the strength of associations to health-related outcomes was comparable or weaker than that of our panel composed only of physical performance measures (CA r = 0.59). All BA estimates were significantly associated to the outcomes considered, with exception to the neurological and musculoskeletal disease domains, and only varied slightly by sex. In summary, while the approximation of CA is important to consider when estimating BA, the strength of associations to prospective outcomes may be of greater importance. Hence, the context in which BA is estimated should be influenced by an investigator's specific research goals., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Maintenance of lung function is an often underappreciated, yet critical component of healthy aging. Given the unprecedented shift in the average age of Canadians over the next half century, it will be important to investigate the determinants of lung function in the elderly. In the following study, we estimated the association between lung function and a broad array of factors related to sociodemographics, lifestyle, chronic medical conditions and psychosocial factors in older adults aged 45-86 years old using cross-sectional data from the Canadian Longitudinal Study of Aging (n = 21,338). In addition to examining the entire cohort, we also performed stratified analyses within men/women, adults aged 45-64/65+, and healthy/comorbid. In multivariable regression, our explanatory factors (excluding age, sex, height and ethnicity) were able to explain 17% and 11% of the total variance in FEV 1 and FEV 1 /FVC, respectively. Notable and significant contributions were observed for respiratory disease, smoking, obesity, income, and physical activity, while psychosocial factors mainly exhibited non-significant associations. Generally, these associations were stronger for males than females, and adults 65 and older as compared to those aged 45-64. Our findings indicate that there are pervasive and generally under-recognized sociodemographic and lifestyle factors that exhibit significant associations with FEV 1 and FEV 1 /FVC in older adults. While implication of causality in these relationships is not possible due to the cross-sectional nature of the study, future work aiming to investigate determinants of lung health in older adults may choose to target these factors, given that many are modifiable., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The most common methods for measuring mobility in older adulthood include performance-based tests, such as the Timed-Up-and-Go and gait speed. While these measures have strong predictive validity for adverse outcomes, they are limited to assessing what older adults do in standardized settings, rather than what they do in their daily life. Life-space mobility, which is the ability to move within environments that expand from one's home to the greater community, has been proposed as a more comprehensive measure of mobility. The aim of this study was to determine the association between modifiable factors and life-space mobility in older adults enrolled in the Canadian Longitudinal Study on Aging (CLSA)., Methods: Life-space mobility was measured using the Life Space Index (LSI). Explanatory factors included physical, psychosocial and cognitive determinants, as well as pain, fatigue, driving status, nutrition, body mass index, smoking status, and vision. To estimate the association between the LSI and explanatory variables, univariate and multivariable ordinary least squares regression analyses were performed., Results: All adults 65 years and older (n = 12,646) were included in the analysis. Fifty percent were women and the mean age was 73.0 (SD5.7). The mean LSI score was 80.5, indicating that, on average, the sample was able to move outside of their neighborhood independently. All explanatory variables were significantly associated with the LSI except for balance and memory. The top 3 variables that explained the most variation in the LSI were driving, social support and walking speed., Conclusion: To our knowledge, this was the first study to examine the association between life-space mobility and a comprehensive set of modifiable factors that were selected based on a theoretical framework and existing research evidence. This study had two important messages. First, driving, social support and walking speed emerged as the most significant correlates of life-space mobility in older adults. Second, life-space mobility is multifactorial and interventions that are pragmatic in their design and testing are needed that consider the complexity involved. A multi-disciplinary approach to examining life-space mobility in older adults is needed to optimize opportunities for healthy aging and develop strategies that support mobility in older adulthood.

Background: The levels of circulating cytokines fluctuate with age, acute illness, and chronic disease, and are predictive of mortality; this is also true for patterns of DNA (CpG) methylation. Given that immune cells are particularly sensitive to changes in the concentration of cytokines in their microenvironment, we hypothesized that serum levels of TNF, IL-6, IL-8 and IL-10 would correlate with genome-wide alterations in the DNA methylation levels of blood leukocytes. To test this, we evaluated community-dwelling adults (n = 14; 48-78 years old) recruited to a pilot study for the Canadian Longitudinal Study on Aging (CLSA), examining DNA methylation patterns in peripheral blood mononuclear cells using the Illumina HumanMethylation 450 K BeadChip., Results: We show that, apart from age, serum IL-10 levels exhibited the most substantial association to DNA methylation patterns, followed by TNF, IL-6 and IL-8. Furthermore, while the levels of these cytokines were higher in elderly adults, no associations with epigenetic accelerated aging, derived using the epigenetic clock, were observed., Conclusions: As a preliminary study with a small sample size, the conclusions drawn from this work must be viewed with caution; however, our observations are encouraging and certainly warrant more suitably powered studies of this relationship.

Monocyte phenotype and output changes with age, but why this occurs and how it impacts anti-bacterial immunity are not clear. We found that, in both humans and mice, circulating monocyte phenotype and function was altered with age due to increasing levels of TNF in the circulation that occur as part of the aging process. Ly6C+ monocytes from old (18-22 mo) mice and CD14+CD16+ intermediate/inflammatory monocytes from older adults also contributed to this "age-associated inflammation" as they produced more of the inflammatory cytokines IL6 and TNF in the steady state and when stimulated with bacterial products. Using an aged mouse model of pneumococcal colonization we found that chronic exposure to TNF with age altered the maturity of circulating monocytes, as measured by F4/80 expression, and this decrease in monocyte maturation was directly linked to susceptibility to infection. Ly6C+ monocytes from old mice had higher levels of CCR2 expression, which promoted premature egress from the bone marrow when challenged with Streptococcus pneumoniae. Although Ly6C+ monocyte recruitment and TNF levels in the blood and nasopharnyx were higher in old mice during S. pneumoniae colonization, bacterial clearance was impaired. Counterintuitively, elevated TNF and excessive monocyte recruitment in old mice contributed to impaired anti-pneumococcal immunity since bacterial clearance was improved upon pharmacological reduction of TNF or Ly6C+ monocytes, which were the major producers of TNF. Thus, with age TNF impairs inflammatory monocyte development, function and promotes premature egress, which contribute to systemic inflammation and is ultimately detrimental to anti-pneumococcal immunity.

Background: To describe T-cell and natural killer (NK) cell phenotypes within nursing home elderly., Methods: Nursing home elderly were recruited from four nursing homes in Hamilton, Ontario between September 2010 and December 2011. Healthy adults were recruited from McMaster University between September 2011 and December 2011. Nursing home elderly ≥65 years were eligible; those on immunosuppressive medications were excluded. Healthy adults ≥18-64 years were eligible. CD8+ and CD4+ T-cells% and their subsets, T-regs% and NK cell subset% were compared between the nursing home elderly and healthy adults., Results: 262 nursing home elderly were enrolled; median age 87 years and 81% were female. 16 healthy adults were enrolled; median age 31 and 50% were female. There was no significant difference between CD8+ T-cell% in nursing home and healthy adults (median 17.1 versus 18.0, p = 0.56), however there were fewer naïve CD8 + T-cell% (median 0.9 versus 5.2, p < 0.001), more terminally differentiated CD8 + T-cell% (median 7.3 versus 4.1, p = 0.004) and more senescent T-cell% (median 5.3 versus 3.1, p = 0.04) in the nursing home elderly. There were more CD4+ T-cell% in the nursing home elderly compared to healthy adults (median 45.5 versus 37.1, p = 0.001). Nursing home elderly had a higher CD4+/CD8+ ratio than healthy adults (2.6 versus 1.9, p = 0.048), higher T-reg% (median 1.8 versus 0.8, p < 0.001) and increased mature NK cell% (median 12.1 versus 5.4, p = 0.001) compared to healthy adults., Conclusion: Differences in naïve CD8+ T-cells, terminally differentiated and senescent CD8+ T-cells, T-regs and NK cell subsets were similar to studies involving community dwelling elderly. In contrast, the CD4+/CD8+ ratio was higher in nursing home elderly.

As we age, the composition of our peripheral leukocytes changes dramatically. Many of these alterations contribute to the general immune dysfunction that burdens the elderly, which in turn, contributes to increased susceptibility to disease. MDSCs represent a heterogeneous population of immunosuppressive leukocytes that are elevated in the peripheral blood of cancer patients. Given the relation between cancer incidence and age, this study examined the frequency of peripheral blood CD33(+)HLA-DR(-) MDSCs across three cohorts: healthy adults (19-59 years old), community-dwelling seniors (61-76 years old), and frail elderly (67-99 years old). This analysis is the first to demonstrate that MDSCs and specifically the CD11b(+)CD15(+) MDSC subset are increased with age. Proinflammatory cytokines that are required for the differentiation of MDSCs (e.g., TNF-α, IL-6, and IL-1β) were similarly found to be increased in the serum of the frail elderly. Furthermore, the proportion of MDSCs and the CD11b(+)CD15(+) subset were found to be elevated significantly in elderly donors with a history of cancer. This age-related elevation in the frequency of MDSCs may contribute to the increased cancer incidence that occurs with age. Further investigation into the functional consequences of elevated MDSCs will provide valuable insight into the progression of age-related pathologies.

As humans age, they experience a progressive loss of thymic function and a corresponding shift in the makeup of the circulating CD8+ T cell population from naïve to memory phenotype. These alterations are believed to result in impaired CD8+ T cell responses in older individuals; however, evidence that these global changes impact virus-specific CD8+ T cell immunity in the elderly is lacking. To gain further insight into the functionality of virus-specific CD8+ T cells in older individuals, we interrogated a cohort of individuals who were acutely infected with West Nile virus (WNV) and chronically infected with Epstein Barr virus (EBV) and Cytomegalovirus (CMV). The cohort was stratified into young (<40 yrs), middle-aged (41-59 yrs) and aged (>60 yrs) groups. In the aged cohort, the CD8+ T cell compartment displayed a marked reduction in the frequency of naïve CD8+ T cells and increased frequencies of CD8+ T cells that expressed CD57 and lacked CD28, as previously described. However, we did not observe an influence of age on either the frequency of virus-specific CD8+ T cells within the circulating pool nor their functionality (based on the production of IFNγ, TNFα, IL2, Granzyme B, Perforin and mobilization of CD107a). We did note that CD8+ T cells specific for WNV, CMV or EBV displayed distinct functional profiles, but these differences were unrelated to age. Collectively, these data fail to support the hypothesis that immunosenescence leads to defective CD8+ T cell immunity and suggest that it should be possible to develop CD8+ T cell vaccines to protect aged individuals from infections with novel emerging viruses.